This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. My laboratory pioneered and successfully demonstrated a novel derivatization strategy via replacement of oxygen of nucleic acids with selenium. Our research is based on the central hypothe selenium can be used to stably replace oxygen of nucleic acids atom-specifically without significant perturbation, because selenium and oxygen are in the same elemental family. We have successfully demonstrated that the selenium derivatization of nucleic acids can be useful to solve the phase problem. Moreover, we have found that the selenium derivatization can facilitate oligonucleotide crystallization. Thus, this Se-derivatization strategy has great potential to provide novel solutions to both long-standing problems: phasing and crystallization, especially for nucleic acids and protein-nucleic acid complexes. Therefore, our structural research focuses on developing general strategies for phasing, crystallization, and crystal structure determination of nucleic acids and protein complexes.